Catalase Gene Variants and Oxidative Stress in Autism Spectrum Disorder: A Northern Lebanon Cohort and Aripiprazole...

Autism spectrum disorder (ASD) is a multifactorial neurodevelopmental condition influenced by genetic, epigenetic and environmental factors. Oxidative stress and antioxidant enzyme polymorphisms, particularly catalase (CAT), have been implicated in ASD, but findings remain inconsistent. In parallel, pharmacological interventions such as aripiprazole, which is widely used in ASD, have cellular toxicological profiles that remain incompletely defined.

A total of 94 participants (39 ASD patients and 55 controls) were genotyped for the CAT polymorphism rs7943316 using tetra-primer amplification refractory mutation system PCR (T-ARMS-PCR). Genotype distributions were statistically compared using χ² and Fisher's exact tests. In vitro toxicological assays were performed in Saccharomyces cerevisiae wild type (BY4741) and mutant strains deficient in oxidative stress and lipid metabolism genes (CAT1, CPT2, PXA2 and FAA1). Yeast growth was quantified under increasing concentrations of aripiprazole, and IC₅₀ values were determined.

Genotype distribution of rs7943316 showed no significant difference between ASD and control groups (p = 0.866), indicating no association between this CAT polymorphism and ASD risk in this Lebanese cohort. Toxicological profiling revealed that aripiprazole caused dose-dependent growth inhibition. Mutant strains lacking CAT1, CPT2 or PXA2 exhibited significantly reduced IC₅₀ values compared to wild type (p < 0.05), highlighting oxidative stress detoxification, carnitine-mediated acetyl-CoA transport and peroxisomal fatty acid import as key determinants of drug sensitivity.

CAT polymorphism rs7943316 is not associated with ASD in this population. However, aripiprazole exerts dose-dependent toxicity strongly modulated by oxidative stress and metabolic pathways. These findings support the integration of genetic and toxicological approaches for understanding ASD and optimizing therapeutic safety.